Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection. Academic Article uri icon

Overview

abstract

  • Daclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) or simeprevir (SMV) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection. Herein, we report efficacy and safety data for DCV-based all-oral antiviral therapy in liver transplantation (LT) recipients with severe recurrent HCV. DCV at 60 mg/day was administered for up to 24 weeks as part of a compassionate use protocol. The study included 97 LT recipients with a mean age of 59.3 ± 8.2 years; 93% had genotype 1 HCV and 31% had biopsy-proven cirrhosis between the time of LT and the initiation of DCV. The mean Model for End-Stage Liver Disease (MELD) score was 13.0 ± 6.0, and the proportion with Child-Turcotte-Pugh (CTP) A/B/C was 51%/31%/12%, respectively. Mean HCV RNA at DCV initiation was 14.3 × 6 log10 IU/mL, and 37% had severe cholestatic HCV infection. Antiviral regimens were selected by the local investigator and included DCV+SOF (n = 77), DCV+SMV (n = 18), and DCV+SMV+SOF (n = 2); 35% overall received RBV. At the end of treatment (EOT) and 12 weeks after EOT, 88 (91%) and 84 (87%) patients, respectively, were HCV RNA negative or had levels <43 IU/mL. CTP and MELD scores significantly improved between DCV-based treatment initiation and last contact. Three virological breakthroughs and 2 relapses occurred in patients treated with DCV+SMV with or without RBV. None of the 8 patient deaths (6 during and 2 after therapy) were attributed to therapy. In conclusion, DCV-based all-oral antiviral therapy was well tolerated and resulted in a high sustained virological response in LT recipients with severe recurrent HCV infection. Most treated patients experienced stabilization or improvement in their clinical status.

authors

  • Fontana, Robert J
  • Brown, Robert S.
  • Moreno-Zamora, Ana
  • Prieto, Martin
  • Joshi, Shobha
  • Londoño, Maria-Carlota
  • Herzer, Kerstin
  • Chacko, Kristina R
  • Stauber, Rudolf E
  • Knop, Viola
  • Jafri, Syed-Mohammed
  • Castells, Lluís
  • Ferenci, Peter
  • Torti, Carlo
  • Durand, Christine M
  • Loiacono, Laura
  • Lionetti, Raffaella
  • Bahirwani, Ranjeeta
  • Weiland, Ola
  • Mubarak, Abdullah
  • ElSharkawy, Ahmed M
  • Stadler, Bernhard
  • Montalbano, Marzia
  • Berg, Christoph
  • Pellicelli, Adriano M
  • Stenmark, Stephan
  • Vekeman, Francis
  • Ionescu-Ittu, Raluca
  • Emond, Bruno
  • Reddy, K Rajender

publication date

  • April 1, 2016

Research

keywords

  • Antiviral Agents
  • Hepatitis C, Chronic
  • Imidazoles
  • Simeprevir
  • Sofosbuvir

Identity

Scopus Document Identifier

  • 84961741466

Digital Object Identifier (DOI)

  • 10.1002/lt.24416

PubMed ID

  • 26890629

Additional Document Info

volume

  • 22

issue

  • 4